Crystal structure of a trimeresurus mucrosquamatus venom metalloproteinase providing new insights into the inhibition by endogenous tripeptide inhibitors.
The crystal structure of TM-1, a P-I class snake-venom metalloproteinase (SVMP)
from the Trimeresurus mucrosquamatus venom, was determined at 1.8-Å
resolution. The structure exhibits the typical feature of SVMPs and is
stabilized by three disulfide linkages. The active site shows a deep S1'
substrate-binding pocket limited by the non-conserved Pro174 at the bottom.
Further comparisons with other SVMPs suggest that the deep S1' site of TM-1
correlates with its high inhibition sensitivity to the endogenous tripeptide
inhibitors. Proteolytic specificity analysis revealed that TM-1 prefers
substrates having a moderate-size and hydrophobic residue at the P1' position,
consistent with our structural observation.
